TY - JOUR T1 - Colonic mucosa-associated diffusely adherent <em>afaC+ Escherichia coli</em> expressing <em>lpfA</em> and <em>pks</em> are increased in inflammatory bowel disease and colon cancer JF - Gut JO - Gut SP - 761 LP - 770 DO - 10.1136/gutjnl-2013-304739 VL - 63 IS - 5 AU - Maelle Prorok-Hamon AU - Melissa K Friswell AU - Abdullah Alswied AU - Carol L Roberts AU - Fei Song AU - Paul K Flanagan AU - Paul Knight AU - Caroline Codling AU - Julian R Marchesi AU - Craig Winstanley AU - Neil Hall AU - Jonathan M Rhodes AU - Barry J Campbell Y1 - 2014/05/01 UR - http://gut.bmj.com/content/63/5/761.abstract N2 - Objective Colonic mucosa-associated Escherichia coli are increased in Crohn's disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA. We investigated genes responsible for these effects and their co-association in colonic mucosal isolates. Design A fosmid library yielding 968 clones was prepared in E coli EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic E coli isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome). Results 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin afa-1 operon. Transfection of afa-1 into E coli K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. E coli expressing afaC were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). E coli expressing both afaC and lpfA (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). E coli expressing both afaC and pks (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed dsbA and htrA relevant to intra-macrophage replication, and 242/281 expressed fimH encoding type-1 fimbrial adhesin. Conclusions IBD and CRC commonly have colonic mucosal E coli that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity. ER -